The present invention relates to a system and method for oxygenation of ischemic heart tissue. In particular, the present invention relates to a system and method for supplying oxygen to the myocardium of the heart through means other than the coronary arteries.
There are an estimated 1.5 million heart attacks recorded annually in the United States alone; of which only 1.2 million (80%) victims reach the hospital alive. Another 300,000 die in the hospital to account for an annual death rate of approximately 600,000.
The 900,000 heart attack or myocardial infarction (MI) victims which do survive, are affected by a significant morbidity rate caused by irreversible damage to the heart, such as scarring of the myocardial tissue.
In addition to the damage caused by heart attacks, patients which undergo percutaneous transluminal coronary angioplasty (PTCA) are at risk of developing iatrogenic myocardial ischemia. In particular, when PTCA is performed, a dilatation balloon is inflated within a coronary artery, thus blocking blood flow to the distal myocardium during the inflation period. It is often desirable to maintain the balloon in an inflated condition for periods up to two minutes or longer, during which time significant ischemia may develop.
In both clinical situations; i.e. MI and PTCA, there is a great need for a system and method of providing oxygen to the myocardial tissue, until such time as reperfusion of blood can be reestablished. In particular, following an MI, there is always a certain time period of non-perfusion during which ischemia may develop. This is especially true during patient transport to the hospital, and until occluded vessels can be reopened by PTCA or thrombolytic agents, for example.
It is generally thought that ischemia caused by non-perfusion periods of 30 minutes or less, is fully reversible with no permanent damage to the heart muscle. Ischemic periods of 30 to 90 minutes will generally cause myocardial stunning and often the heart fails to completely recover or does so over a relatively long period of time. If non-perfusion occurs for periods beyond 2 to 4 hours, the ischemia which develops will generally result in the death of the unperfused myocardial portions.
In order to keep ischemia to a minimum, typical PTCA procedures employ balloon inflation times of only 30 to 60 seconds. Longer periods of inflation are possible by monitoring the ischemia qualitatively by means such as an electrocardiogram recording. Relatively recent approaches of supplying oxygen to the myocardial tissue during PTCA, include perfusing oxygenated blood or perfluorocarbon emulsions through a central lumen of the PTCA catheter. Such techniques have been reported in several journals including Nunn et al, Am. J. Cardiol., 52:203-205, 1983; Kolodgie et al, Am. Heart J., 112:1192-1201, 1986; Glogar et al, Science, 211:1439-1441, 1981. Further, in cases of PTCA following an MI, intravenous introduction of perfluorocarbons has been used to reoxygenate the myocardium. However, such is possible only when blood flow has already been reestablished through stenosed or thrombus blocked vessels.
The administration of thrombolytic agents either intravenously or directly into the coronary arteries is another means of reopening blocked vessels. Thrombolytic agents work by dissolving the occluding thrombus and thereby reestablishing blood flow. When thrombolytic agents are administered properly, they can be expected to restore blood flow relatively quickly in cases of minor MIs. However, in cases of massive MIs, or in cases of delayed administration, the efficacy of the agents can be drastically reduced. Further, there are several disadvantages associated with the use of thrombolytic agents, such as the selection of proper dose, hemorrhagic side effects, delayed dissolving action of 30 to 60 minutes or more, short half life in the blood, and expense. In addition, not all patients are suitable candidates for the use of thrombolytic agents based on factors such as age, bleeding conditions, etc.
Delays in reperfusion of the myocardium following an MI give rise to physiological and biochemical changes in the ischemic tissue and in the white blood cells. These changes may trigger the release of oxygen free radicals during the first few minutes following reestablishment of blood flow. The free radicals can add further damage to the already at risk ischemic tissue.
Several drugs have been studied as possible blockers of reperfusion damage to the heart. Many of these have shown effectiveness after intravenous or intracoronary administration. In particular, the administration of perfluorochemical emulsions have been shown to be of potential value in preventing reperfusion damage when used at the time of reperfusion. (See Forman et al, J. Am. Coll. Cardiol., 9:1082-1090, 1987; Roberts et al, Am. J. Cardiol., 57:1202-1205, 1986; Bajaj et al, Circulation, 79:645-656, 1989.) It is believed that this damage prevention arises from the ability of perfluorochemicals to carry oxygen to the tissue, to scavenge any released oxygen radicals, and to flush white blood cells from the reperfused segments.
However, all of the methods and drugs mentioned above, suffer from the same disadvantage that their effectiveness is dependent on the reopening of blocked vessels. In particular, all of the prior art methods are carried out by intravenous or intracoronary administration which necessarily requires the reopening of blocked vessels to deliver the drugs to the at risk myocardium.
Therefore, there is a great need for a system and method which can be used to supply oxygen to the myocardium by means other than through the coronary arteries.
One study examined the administration of oxygen gas into the pericardial space as means of providing some protection against ischemia produced by ligation of the left anterior descending coronary artery. (See Sedlarik et al, Res. Exp. Med. (Berl), 183:177-181, 1983.) Efficacy of this method was apparently based on the uptake and transport of oxygen by the lymphatic channels. However, there are many risks in such a procedure, such as, difficulty in controlling the administration of a gas, inability to accurately monitor the administration by ultrasound, potential of gas embolism formation and consequent dangers of removal, drying of the tissue by the gas, and the inability to remove carbon dioxide thus giving rise to acidosis. In addition, administration of oxygen as a gas does not allow the concurrent administration of therapeutic drugs or nutrients.
Therefore, there is also a great need to provide a system and method of which can be used to supply oxygen to the myocardium by means other than through the coronary arteries and which avoids the drawbacks of using a gas.